The currently used live, attenuated measles vaccine is one of the most safe and effective vaccines available worldwide. However, because maternal antibody can neutralize the vaccine virus in the vaccinated infant, it cannot be administered before 6 to 9 months of age. This leaves a population of infants in inner cities of the U.S. and in developing countries vulnerable to measles, which has high rates of morbidity and mortality at this young age. The goal of this project is to develop a safe and effective vaccine for measles virus that can be given orally or intranasally at birth. Newborn rhesus monkeys were inoculated with recombinant Bacille Calmette Guerin (BCG) by the intradermal or intranasal routes. The recombinant BCG was 1 a control vector (n = 4), 2 expressed measles nucleoprotein (NP) as an extrachromosomal plasmid (n = 4), or 3 expressed an integrated copy of measles NP (n = 4). Live BCG containing the measles NP insert was recovered from draining lymph nodes up to 3 months after intradermal inoculation. The infants were given a booster dose of BCG at 3 months after the first dose. These infants will be challenged intranasally with pathogenic measles virus at 4 months after the booster. Immunity to the vector was detected by Mantoux skin tests at 2 months after the first vaccine. Antibody and T cell proliferative responses to measles NP were negative after the first vaccine, but weak proliferative responses to NP were detectable after the second dose. The major aim is to prevent serious disease or death, but not primary infection, in challenged infants.